Nature - USA (2019-07-18)

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nature research | reporting summary

April 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

All data will be made available from the authors upon reasonable request. The described RNA-seq and ChIP–seq and ATAC-seq data will be deposited in the Gene

Expression Omnibus in the future.

Field-specific reporting

Please select 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/authors/policies/ReportingSummary-flat.pdf

Life sciences study design

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

Sample size No sample size calculation was done, for most assays, 3 biological replicates were carried out. For organoid lines, there are often more than 3

because lines were often included in a replicate experiment before results of previous experiment was analyzed, resulting in a greater number

of replicates than what was likely needed.

Data exclusions Entire growth assays were excluded if the control line did not grow as expected (i.e. didn't recover well from sorting so there was no growth

seen). In that situation, data from entire experiment (all lines) were excluded. Mouse tumor measurements were excluded from data if it was

noted at the time of injection that there was a technical issue. Both of these circumstances were pre-established and were held true for all

lines.

Replication All findings were reproducible, as more than 1 biological replicate was generally carried out, or the sample sizes were large enough to ensure

good representation of the population behavior.

Randomization No randomization was done for our experiments because there were no drug treatment groups, and all work was done in vitro.

Blinding For lumen size assays, actual measurements were carried out by a member of the lab who did not have any knowledge of which alleles were

associated with growth/lumen formation phenotypes. All other experiments were not blinded and it was not necessary to be as they were

much more quantitative and less subjective.

Reporting for specific materials, systems and methods

Materials & experimental systems

n/a Involved in the study

Unique biological materials

Antibodies

Eukaryotic cell lines

Palaeontology

Animals and other organisms

Human research participants

Methods

n/a Involved in the study

ChIP-seq

Flow cytometry

MRI-based neuroimaging

Unique biological materials

Policy information about availability of materials

Obtaining unique materials All unique materials are readily available upon request.