Nature - USA (2019-07-18)

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nature research | reporting summary

October 2018

Data

Policy information about availability of data

All manuscripts must include a data availability statement. This statement should provide the following information, where applicable:

• Accession codes, unique identifiers, or web links for publicly available datasets


• A list of figures that have associated raw data


• A description of any restrictions on data availability

RNA sequencing data is publicly available through ArrayExpress (http://www.ebi.ac.uk/arrayexpress/experiments/E-MTAB-7916). All other data are available from

the corresponding author upon reasonable request.

Field-specific reporting

Please select the one below that is the best fit for your research. If you are not sure, read the appropriate sections before making your selection.

Life sciences Behavioural & social sciences Ecological, evolutionary & environmental sciences

For a reference copy of the document with all sections, see nature.com/documents/nr-reporting-summary-flat.pdf

Life sciences study design

All studies must disclose on these points even when the disclosure is negative.

Sample size Sample size was not predetermined with any statistical test. Sufficient sample sizes were estimated based on previous experiments with the

same system.

Data exclusions Outliers in Extended Data Fig. 4e and Extended Data Fig. 5l were removed from statistical analysis based on deviating >2 s.d. from the rest.

Outliers are marked red in the corresponding figures. Cut-off of 2 s.d. was applied to all data of similar type, but exclusion criteria was not pre-

set. No other data was excluded for other reasons than for being technically inadequate or unusable due to mistakes.

Replication All experiments were successfully reproduced with biological replicates or independent technical replicates, except data in Extended Data Fig.

1o , where only three replicates from the same mouse were performed with similar results and in Extended Data Fig. 2d where KO validation

was performed only once for the organoid line used in Extended Data Fig. 2e.

Randomization Animals were allocated to experimental groups randomly, but no formal randomization were performed

Blinding All histological analysis were performed by blinded investigator. In vitro quantifications were analyzed by blinded investigator when possible,

but due to features of co-culture experiments this was not always possible. For animal work, investigators were not blinded due to evident

external phenotype of aged mice.

Reporting for specific materials, systems and methods

We require information from authors about some types of materials, experimental systems and methods used in many studies. Here, indicate whether each material,

system or method listed is relevant to your study. If you are not sure if a list item applies to your research, read the appropriate section before selecting a response.

Materials & experimental systems

n/a Involved in the study

Antibodies

Eukaryotic cell lines

Palaeontology

Animals and other organisms

Human research participants

Clinical data

Methods

n/a Involved in the study

ChIP-seq

Flow cytometry

MRI-based neuroimaging

Antibodies

Antibodies used CD31-PE, Biolegend, Mec13.3, 1:500

CD45-PE, eBioscience, 30-F11, 1:500

Ter-119-PE, Biolegend, Ter119, 1:500

CD24-PacificBlue, Biolegend, M1/69, 1:500

Epcam-APC, eBioscience, G8.8, 1:500

Olfm4 (clone PP7), gift from CST in Fig 1d, 1:300

Olfm4, CST, 39141 in Fig 3f, 1:300